Indian Pediatr 2011;48: 565-567
Congenital Myotonic Dystrophy with
KM Anand, VM Biradar, JN Panicker* and Sheela Nampoothiri†
From the Department of Neonatology, Lakshmi Hospital,
Cochin; and *Rehabilitation Center, and †Pediatric Genetics, Amrita
Institute of Medical Sciences and Research Center, Cochin, Kerala, India.
Correspondence to: Dr KM Anand, Consultant Neonatologist,
Sunrise Hospital, Kochi, Kerala, India.
Received: December 8, 2009;
Review completed: December 28, 2009;
Accepted: April 6, 2010.
Myotonic dystrophy is an autosomal dominant neuromuscular disorder
characterised by extreme pleiotropism and variability in disease
expression. A congenital form is rare and is observed in infants born to
symptomatic mothers with multisystem involvement. We report a case of a
neonate with congenital myotonic dystrophy born to an asymptomatic
Key Words: Asymptomatic mother, Congenital Myotonic dystrophy,
Diaphragmatic weakness, Floppy infant.
yotonic dystrophy (DM) is the most common inherited
neuromuscular disorder with a prevalence of 1:8000 . It is caused
by a triplet repeat expansion (CTG) in the non-coding region of the
myotonin gene at 19q13.3. The typical form has an onset in early
adult life and is characterised by myotonia, skeletal muscle
weakness and wasting, cardiac conduction defects, and cataracts. We
report an infant with genetically proven congenital myotonic
dystrophy, the diagnosis of which was clinched by the combination of
generalised floppiness and diaphragmatic weakness.
The proband was born via caesarean section to
non-consanguineous parents at 32 weeks of gestation, which was
complicated, by polyhydramnios and breech presentation. Baby cried
immediately after birth. The couple had a previous first trimester
mis-carriage. Baby was admitted to neonatal intensive care unit
following mild respiratory distress. Physical examination revealed
severe tachypnoea, generalised floppiness, cold peripheries,
microcephaly, narrow palpebral fissure, antimongoloid slant, low set
ears and bilateral simian crease.
Blood parameters including complete blood count,
electrolytes, blood urea, serum creatinine and C reactive protein
were all within normal limits. Chest radiograph showed bilateral
high domes of diaphragm. Based on sudden unexplained respiratory
failure and radiographic findings, possibility of a neuromuscular
disorder was considered.
Electrophysiological studies were not done as the
baby was on ventilator. Care was withdrawn on day 2 of life after
discussing with the parents, as the ventilatory requirements were
very high and the prognosis was grim. Echocardiogram and
electro-cardiogram were normal. DNA from the baby was subjected to
Southern blot analysis. The baby was found to be heterozygous as the
number of CTG repeats in one of the alleles was >700 (normal 4-37
repeats) whereas in the other allele, the repeat size was only 4.
This confirmed the diagnosis of congenital myotonic dystrophy in the
baby. Karyo-type of the baby was 46XX.
Both parents were apparently healthy and did not
show any classical symptoms of neuromuscular disorders. However, on
examination, mother had mini-mal percussion myotonia of thenar
muscles and tongue. Electromyography of the mother revealed myotonia
from all tested muscles of upper and lower limbs. Her CPK levels
were 92 U/L, fasting blood sugar was 92 mg/dl and TSH level was 3.23
uIU/L. Ophthalmological evaluation revealed bilateral early
cataracts. Southern blot analysis of the mother showed >300 repeats
from one allele and 13 repeats from the other allele. This confirmed
that the mother is also affected with myotonic dystrophy.
DM is characterised by extreme variability,
anticipation and differential expansion in the maternal and paternal
germline, so much so that congenital myotonic dystrophy (CDM) is
always transmitted from the maternal allele. The usual number of
repeats is 4-37. The repeat number goes up to 200-500 in classical
myotonia and in CDM the CTG repeat are usually >1000 .
CDM was first described in 1960 and is the
most severe phenotypic expression of DM1 . Congenital form is
frequently fatal and is usually observed in infants born to
classically affected mothers. One interesting feature in this case
is the fact that mother was totally asymptomatic. The explanation
for selective maternal transmission as the major cause for CDM is
that mature spermatozoa can carry only small expansions whereas ova
can accommodate much larger expansions. Koch, et al.
found that only women with multisystem signs of DM1 at the time of
pregnancy and delivery were likely to have congenitally affected
offspring and that the chance of having a more severely affected
child increased with maternal disease severity [3,4]. These
observations have been supported by more recent molecular studies
which showed that infants with CDM and their mothers had greater
amplification of the CTG repeats than those with non-CDM and their
mothers and the maternal expansion was three times greater in the
CDM group than in the non-CDM group [5,6].
The differentials include congenital muscular
dystrophy, neonatal myasthenic syndrome, congenital myopathy and
spinal muscular atrophy with respiratory distress type 1. Congenital
muscular dystrophies are characterized by hypotonia and need at
birth or shortly thereafter with multiple joint contractures.
Neonatal myasthenic syndromes includes familial myasthenia with
prominent respiratory and feeding difficulty at birth, and
congenital myasthenia with predominant ocular findings. Congenital
myopathies presenting as neonatal hypotonia needs muscle biopsy for
confirmation. Spinal muscular atrophy with respiratory distress type
1(SMARD1) is a distinct genetic disorder and these babies are
usually born with intrauterine growth retardation with a weak cry,
and foot deformities . Polyhydraminos and reduced foetal
movements are two important ultrasound markers that should alert the
clinician to consider the diagnosis of CDM. In a mother with 200-500
repeats and with a previous child with CDM, the risk or recurrence
is 40-50% . The mother was counselled regarding the prospects of
prenatal diagnosis in her future pregnancy by determination of CTG
expansion in the fetus by chorionic villus sampling or
The diagnosis of congenital myotonic dystrophy is
often difficult in babies whose parents are not diagnosed. The lack
of family history in a baby with severe manifestation has only been
rarely reported in literature . The number of trinucleotide
repeats is known to predict the degree of muscular disability in DM
, but as shown here, may not correlate with individual clinical
Contributors: KMA was involved in patient
management, conception and design of study, analysis of data, SN has
done the genetic work up and confirmed the diagnosis and has
critically reviewed and modified the manuscript. JP has evaluated
the mother and has helped in drafting the manuscript. VMB is
involved in acquisition and interpretation of data, drafting of
manuscript and review of literature.
Competing interests: None stated.
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